拉斯维加斯赌城

图片

The function of tyrosine phosphatases in the regulation of endothelial activation and inflammation

As a first line of defence in inflammatory conditions, cellular components of the innate immunity release pro-inflammatory cytokines. The endothelium, lining the vessels and constituting the barrier between blood and tissue, becomes activated by these inflammatory factors, resulting in for instance the upregulation of adhesion molecules, generation of reactive oxygen species (ROS) and increased vascular permeability. The activation of the endothelium results in the recruitment of inflammatory cells and increased vascular leakage. These responses contribute to tissue oedema and organ failure in systemic inflammatory conditions, such as sepsis or SIRS (systemic inflammatory response syndrome). In chronic inflammatory settings, this promotes endothelial dysfunction and subsequent cardiovascular disease. We have demonstrated the tyrosine phosphatase SHP-2 to be inactivated in endothelial cells under inflammatory conditions, resulting in increased expression of ICAM-1 and VCAM-1 and subsequently in enhanced endothelial leukocyte recruitment and transmigration in vitro and in vivo. Importantly, re-installing SHP-2 activity prevented these inflammatory changes. Moreover, we found inflammatory vascular permeability to be enhanced in mice treated with an SHP-2 inhibitor, pointing towards a protective role of SHP-2 in this context. These data demonstrate that an inactivation of SHP-2 may indeed drive endothelial dysfunction and promote vascular events. Ongoing projects aim to further characterize the underlying mechanisms and direct targets of SHP-2 within this context as well as investigating the function of SHP-2 in endothelial activation and dysfunction in cardiovascular disease under insulin resistant conditions mimicking type 2 diabetes.

?
?

Role of SHP-2 in IL-β dependent endothelial cell signalling and vascular inflammation

Upon inflammatory activation by IL-1β, the adaptor protein MyD88 is phosphorylated on Y257 enabling binding of SHP-2. The binding of SHP-2 results in dephosphorylation of other tyrosine residues and inhibition of downstream signalling. However, inflammation-induced generation of ROS inactivate SHP-2 and consequently cause recruitment of p85/PI3-K to MyD88 and subsequent activation of inflammatory downstream signalling. ICAM-1 and VCAM-1 surface expression is upregulated leading to leukocyte recruitment and vascular leakage is enhanced. In experiments, the forced expression of an inactive SHP-2 protein (CS) or SHP-2 inhibition by PTPI IV enhances the inflammatory response, whereas expression of a constitutively active SHP-2 (EA) prevents this. Figures and illustration are adapted from our publication Heun et al., eBioMedicine, 2019 used under CC-BY-NC-ND 4.0

?

Publications within this subject:?

Heun Yvonn, Pircher Joachim, Czermak Thomas, Bluem Philipp, Hupel Georg, Bohmer Monica, Kraemer Bjoern F., Pogoda Kristin, Pfeifer Alexander, Woernle Markus, Ribeiro Andrea, Hübner Max, Kreth Simone, Claus Ralf A., Weis Sebastian, Ungelenk Luisa, Kr?tz Florian, Pohl Ulrich, Mannell Hanna. Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in sepsis. https://doi.org/10.1016/j.ebiom.2019.03.034
PDF | BibTeX | RIS | DOI
Grundler Groterhorst Katharina, Mannell Hanna, Pircher Joachim, Kraemer Bjoern F.. Platelet proteasome activity and metabolism is upregulated during bacterial sepsis. https://doi.org/10.3390/ijms20235961
PDF | BibTeX | RIS | DOI
Koch Elisabeth, Pircher Joachim, Czermak Thomas, Gaitzsch Erik, Alig Stefan, Mannell Hanna, Niemeyer Markus, Kr?tz Florian, W?rnle Markus. The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular haemostasis in TNFα-induced inflammation in vivo. https://doi.org/10.1155/2013/279781
PDF | BibTeX | RIS | DOI

Functional role of endothelial tyrosine phosphatases in angiogenesis in vitro and in vivo

The formation of new blood vessels (angiogenesis) plays an essential role not only in physiological processes such as development (embryogenesis) and wound healing, but also in pathophysiological processes such as tumour growth and diabetic retinopathy. A condition, which is a strong inducer of angiogenesis is hypoxia. Hypoxia induces the accumulation and activation of the α subunit of the transcription factor hypoxia inducible factor 1 (HIF-1), which is otherwise rapidly degraded by the proteasome under normoxic conditions. HIF-1 induces expression of several angiogenic genes, thus being the target for therapeutic strategies. We found that downregulation of the tyrosine phosphatase SHP-1 enhanced HIF-1α accumulation and increased hypoxia induced VEGF expression as well as endothelial cell (EC) proliferation. Interestingly, we previously showed that the SHP-1 homologue SHP-2 is additionally important for angiogenesis. In contrast to SHP-1, down regulation or inhibition of SHP-2 impairs growth factor mediated EC proliferation, migration and vessel sprouting in vitro and ex vivo. In follow-up projects, we observed that overexpression of an inactive SHP-2 mutant in EC under hypoxia led to reduced HIF-1α accumulation and activity, demonstrating that SHP-2 activity is essential for HIF-1α activity. Moreover, we were able to modulate hypoxic wound healing angiogenesis in vivo by site-directed gene transfer using magnetic lentiviruses expressing different SHP-2 constructs. Whereas introduction of an inactive SHP-2 mutant impaired wound healing angiogenesis, expression of a constitutively active SHP-2 mutant accelerated this. We found that SHP-2 promotes hypoxic angiogenesis by preventing HIF-1α degradation via a Src dependent mechanism. In a further study, we detected that SHP-2 influences 26S proteasomal activity under hypoxia in vitro and in vivo. We are now interested in studying the mechanism of SHP-2 dependent regulation of proteasomal activity under hypoxia in more detail as well as a possible role for SHP-2 in hypoxia dependent vascular permeability and the identification of the underlying mechanisms. Additionally, ongoing projects investigate the role of SHP-2 for angiogenesis and HIF-1α activity under insulin resistant conditions.

?
?

SHP-2 activity promotes hypoxic angiogenesis via HIF-1α activation

SHP-2 is activated under hypoxic conditions and inhibits the proteasomal degradation of HIF-1α via activation of Src signalling. This leads to accumulation of HIF-1α, its subsequent nuclear translocation and increased DNA-binding activity with expression of angiogenic target genes and subsequent hypoxic angiogenesis and wound healing. A) HIF-1α protein levels in EC expressing SHP-2 inactive (CS), constitutively active (E76A) and wildtype (WT) mutants. B) Proteasomal degradation of HIF-1α in wounds of the dorsal skin assessed by HIF1-ODD reporter gene expression. C) Wound healing angiogenesis upon expression of SHP-2 mutant constructs. Graphs and pictures are from our publications Heun et al., IJMS, 2019 (B) used under CC-BY 4.0 and Heun et al., Mol Ther, 2017 (A, C) used under CC-BY-NC-ND 4.0.
?

?

Publications within this subject:?

Mannell Hanna, Kameritsch Petra, Beck Heike, Pfeifer Alexander, Pohl Ulrich, Pogoda Kristin. Cx43 promotes endothelial cell migration and angiogenesis via the tyrosine phosphatase SHP-2. https://doi.org/10.3390/ijms23010294
PDF | BibTeX | RIS | DOI
Heun Yvonn, Grundler Groterhorst Katharina, Pogoda Kristin, Kraemer Bjoern F., Pfeifer Alexander, Pohl Ulrich, Mannell Hanna. The phosphatase SHP-2 activates HIF-1α in wounds in vivo by inhibition of 26S proteasome activity. https://doi.org/10.3390/ijms20184404
PDF | BibTeX | RIS | DOI
Rieck Sarah, Heun Yvonn, Heidsieck Alexandra, Mykhaylyk Olga, Pfeifer Alexander, Gleich Bernhard, Mannell Hanna, Wenzel Daniela. Local anti-angiogenic therapy by magnet-assisted downregulation of SHP2 phosphatase. https://doi.org/10.1016/j.jconrel.2019.05.031
BibTeX | RIS | DOI
Heun Yvonn, Pogoda Kristin, Anton Martina, Pircher Joachim, Pfeifer Alexander, Woernle Markus, Ribeiro Andrea, Kameritsch Petra, Mykhaylyk Olga, Plank Christian, Kroetz Florian, Pohl Ulrich, Mannell Hanna. HIF-1α dependent wound healing angiogenesis in?vivo can be controlled by site-specific lentiviral magnetic targeting of SHP-2. https://doi.org/10.1016/j.ymthe.2017.04.007
PDF | BibTeX | RIS | DOI
Alig Stefan K., Stampnik Yvonn, Pircher Joachim, Rotter Raffaela, Gaitzsch Erik, Ribeiro Andrea, W?rnle Markus, Kr?tz Florian, Mannell Hanna. The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α) protein levels in endothelial cells under hypoxia. https://doi.org/10.1371/journal.pone.0121113
PDF | BibTeX | RIS | DOI
Mannell Hanna, Hellwig Nicole, Gloe Torsten, Plank Christian, Sohn Hae-Young, Groesser Leopold, Walzog Barbara, Pohl Ulrich, Kr?tz Florian. Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo. https://doi.org/10.1159/000110081
BibTeX | RIS | DOI
Mannell Hanna, Hammitzsch Ariane, Mettler Ramona, Pohl Ulrich, Kr?tz Florian. Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt. https://doi.org/10.1016/j.cellsig.2009.09.015
BibTeX | RIS | DOI
Mannell Hanna, Krotz Florian. SHP-2 regulates growth factor dependent vascular signalling and function. https://doi.org/10.2174/1389557514999140506094738
BibTeX | RIS | DOI
Mannell Hanna, Krotz Florian. The role of SHP-2 in cell signalling and human disease. https://doi.org/10.2174/157340807782330264
BibTeX | RIS | DOI

Function of cytohesins in the vascular system

The family of cytohesins, which are small guanine nucleotide exchange factors (GEFs), consisting of cytohesin-1, cytohesin-2 (ARNO), cytohesin-3 (Grp-1) and cytohesin-4, has been shown to contribute to cellular adhesion and transmigration of leukocytes as well as adhesion and migration of other cell types. They also seem to play an important role in insulin signalling. In earlier studies, we demonstrated that inhibition of cytohesin-2 (ARNO) reduced vascular leakage in vivo. We discovered that ARNO directly affects VEGFR-2 signalling in endothelial cells by controlling internalization and degradation of VEGFR-2. Furthermore, we discovered that ARNO is important for the phenotypic switch of vascular smooth muscle cells (VSMC). We found that an inhibition or inactivation of ARNO affected the morphology, reduced the synthetic activity and migration of VSMC induced by the adipokine resistin. Furthermore, ARNO was shown to be important for resistin dependent MMP-2 production as well as migration through activation of the JNK/AP-1 pathway and p38 MAPK. An ongoing project aims to characterize the function of the cytohesins 1, -2, -3 and -4 in hypoxia induced permeability and angiogenesis in endothelial cells.

?
?

Role of ARNO (cytohesin-2) in endothelial cells and vascular smooth muscle cells

In endothelial cells (EC) ARNO stabilizes surface VEGFR-2 thereby promoting VEGFR downstream signalling, leading to proliferation and EC permeability. In vascular smooth muscle cells (VSMC), ARNO promotes the production of MMP-2, the phenotypic switch and migration of these cells via activation of p38 MAPK and JNK, therefore potentially contributing to the formation of atherosclerotic plaques.?

?

Publications within this subject:?

Heun Yvonn, Gr?ff Pascal, Lagara Aikaterini, Schelhorn Romina, Mettler Ramona, Pohl Ulrich, Mannell Hanna. The GEF cytohesin-2/ARNO mediates resistin induced phenotypic switching in vascular smooth muscle cells. https://doi.org/10.1038/s41598-020-60446-z
PDF | BibTeX | RIS | DOI
Mannell Hanna, Pircher Joachim, Chaudhry Daniel I., Alig Stefan K.C., Koch Elisabeth G., Mettler Ramona, Pohl Ulrich, Kr?tz Florian. ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression. https://doi.org/10.1093/cvr/cvr265
BibTeX | RIS | DOI

Mechanisms of endothelial activation induced by cardiopulmonary bypass

Cardiopulmonary bypass (CPB) is routinely used in cardiac surgery because it allows temporary suppression of cardiac activity while keeping systemic circulation maintained by redirecting the blood from the heart and lungs and instead pump it through an extra-corporal circuit. Several components of the CPB process, such as the shear forces generated by the pumps, hemodilution, exposure of blood to the artificial surfaces of the circuit and the aortic cross clamping may contribute to the induction of a systemic inflammatory response. Moreover, the CPB may influence the pharmacodynamics of administered drugs. The inotropic drug levosimendan is often used as therapeutic approach perioperatively in cardiac surgery patients with CPB to improve hemodynamic stabilization and to reduce the risk of post-surgical low cardiac output syndrome. In cooperation with the Department of Pharmacy, LMU, we recently established a LS-ESI-MS/MS protocol for therapeutic drug monitoring (TDM) of levosimendan and its metabolites OR-1855 and OR-1896, enabling rapid and simultaneous detection of these compounds in serum. Subsequently, in cooperation with the Department of Anaesthesiology at the LMU University Hospital we detected low total serum concentrations as well as unbound fractions of these compounds in cardiac surgery patients with CPB. Moreover, we investigated the effects of levosimendan and its metabolites on inflammatory endothelial activation and found levosimendan and both metabolites to reduce reactive oxygen species, while only levosimendan impaired endothelial adhesion molecule upregulation. An ongoing study investigates if the low concentrations of levosimendan and metabolites, which were measured in cardiac surgery patients, still have protective effects on endothelial activation and vascular permeability. We are furthermore interested in studying the underlying cellular mechanisms for the enhanced endothelial barrier disruption and endothelial activation and dysfunction in patients with CPB.

?

Publications within this subject:

Kipka Hannah, Liebchen Uwe, Hübner Max, H?fner Georg, Frey Otto, Wanner Klaus T., Kilger Erich, Hagl Christian, Tomasi Roland, Mannell Hanna. Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass. https://doi.org/10.3389/fcvm.2024.1406338
PDF | BibTeX | RIS | DOI
Kipka Hannah, Schaflinger Rebecca, Tomasi Roland, Pogoda Kristin, Mannell Hanna. The effects of the levosimendan metabolites OR-1855 and OR-1896 on endothelial pro-inflammatory responses. https://doi.org/10.3390/biomedicines11030918
PDF | BibTeX | RIS | DOI
Kipka Hannah, Tomasi Roland, Hübner Max, Liebchen Uwe, Hagl Christian, Wanner Klaus T., Mannell Hanna, H?fner Georg. Simultaneous LC-ESI-MS/MS quantification of levosimendan and its metabolites for therapeutic drug monitoring of cardiac surgery patients. https://doi.org/10.3390/pharmaceutics14071454
PDF | BibTeX | RIS | DOI

Establishment and implementation of local vascular gene transfer by magnetic targeting

Gene delivery to cells constitutes an efficient way to specifically modulate signalling pathways and is a promising approach to induce physiological responses (gene therapy) in both research and medical therapy. Regarding the vasculature, local gene therapy shows great potential in improving ischemic cardiovascular disease and wound healing, but also to inhibit tumor growth and diabetic retinopathy, to mention a few. Upon intravascular application, gene vectors are distributed systemically and apart from reaching the organ of interest, they are also delivered to other sites, causing undesired side-effects. Other hurdles with this technique yet to overcome are poor gene delivery and expression efficiency at the desired site. We have developed an innovative effective gene delivery approach for in vivo use, which combines high efficiency and site-specificity following intravascular application. By using lipid microbubbles coated with superparamagnetic nanoparticles (magnetic microbubbles, MMB) which are associated to lentiviruses, DNA vectors, or AS-ODN we were able to target these to vessels at a specific site in vivo by applying an external magnetic field and subsequent ultrasound mediated disruption of the MMB ("Ultrasound-Targeted Microbubble Destruction"; UTMD) to enable the delivery of their cargo.?This resulted in high transgene expression at the targeted site, whereas the non-specific delivery at other sites was strongly reduced. We further established a technique to efficiently deliver genes to wounds in the dorsal skin of mice to study hypoxic wound healing angiogenesis by using magnetic nanoparticle associated lentiviruses and external magnetic fields. This technique now enables the investigation of cellular mechanisms during vascular regeneration and vascular remodelling in the intact organ.

?
?

Local vascular gene transfer by magnetic targeting

1A) Lipid microbubbles (MB) coated with magnetic nanoparticles (MNP) and lentiviruses (LV) or plasmid-DNA (pDNA) vectors were injected intravascularly and 1B) targeted to a specific site or target tissue by application of an external magnetic field in combination with ultrasound to disrupt the microbubbles. 1C) High transgene expression was observed at the target site, whereas the non-specific transgene expression in other non-targeted tissues was decreased, reducing off-target effects. 2A) By using lentiviruses associated to magnetic nanoparticles (LV-MNP) and an external magnet (MF), transgene expression was directed specifically to wounds in the dorsal skin fold chamber of mice. In this way, hypoxic angiogenesis as well as underlying important cellular mechanisms could be studied and compared to untreated tissue within the same animal. Graphs and pictures are adapted and modified from our publications Heun et al., Theranostics, 2017 (1B, 1C) used under CC BY-NC 4.0 and Heun et al., Mol Ther, 2017 (2A) used under CC-BY-NC-ND 4.0.

?

Publications within this subject:?

Heun Yvonn, Pogoda Kristin, Anton Martina, Pircher Joachim, Pfeifer Alexander, Woernle Markus, Ribeiro Andrea, Kameritsch Petra, Mykhaylyk Olga, Plank Christian, Kroetz Florian, Pohl Ulrich, Mannell Hanna. HIF-1α dependent wound healing angiogenesis in?vivo can be controlled by site-specific lentiviral magnetic targeting of SHP-2. https://doi.org/10.1016/j.ymthe.2017.04.007
PDF | BibTeX | RIS | DOI
Heun Yvonn, Hildebrand Staffan, Heidsieck Alexandra, Gleich Bernhard, Anton Martina, Pircher Joachim, Ribeiro Andrea, Mykhaylyk Olga, Eberbeck Dietmar, Wenzel Daniela, Pfeifer Alexander, Woernle Markus, Kr?tz Florian, Pohl Ulrich, Mannell Hanna. Targeting of magnetic nanoparticle-coated microbubbles to the vascular wall empowers site-specific lentiviral gene delivery in vivo. https://doi.org/10.7150/thno.16192
PDF | BibTeX | RIS | DOI
Mannell Hanna, Pircher Joachim, Fochler Franziska, Stampnik Yvonn, R?thel Thomas, Gleich Bernhard, Plank Christian, Mykhaylyk Olga, Dahmani Chiheb, W?rnle Markus, Ribeiro Andrea, Pohl Ulrich, Kr?tz Florian. Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles. https://doi.org/10.1016/j.nano.2012.03.007
BibTeX | RIS | DOI
Mannell Hanna, Pircher Joachim, R?thel Thomas, Schilberg Katharina, Zimmermann Katrin, Pfeifer Alexander, Mykhaylyk Olga, Gleich Bernhard, Pohl Ulrich, Kr?tz Florian. Targeted endothelial gene delivery by ultrasonic destruction of magnetic microbubbles carrying lentiviral vectors. https://doi.org/10.1007/s11095-012-0678-8
BibTeX | RIS | DOI
Rieck Sarah, Heun Yvonn, Heidsieck Alexandra, Mykhaylyk Olga, Pfeifer Alexander, Gleich Bernhard, Mannell Hanna, Wenzel Daniela. Local anti-angiogenic therapy by magnet-assisted downregulation of SHP2 phosphatase. https://doi.org/10.1016/j.jconrel.2019.05.031
BibTeX | RIS | DOI
R?thel T., Mannell Hanna, Pircher Joachim, Gleich B., Pohl Ulrich, Kr?tz F.. Magnetic stents retain nanoparticle-bound antirestenotic drugs transported by lipid microbubbles. https://doi.org/10.1007/s11095-011-0643-y
BibTeX | RIS | DOI
Gleich Bernhard, Hellwig Nicole, Bridell Hanna, Jurgons Roland, Seliger Christian, Alexiou Christoph, Wolf Bernhard, Weyh Thomas. Design and evaluation of magnetic fields for nanoparticle drug targeting in cancer. https://doi.org/10.1109/tnano.2007.891829
BibTeX | RIS | DOI

Publikationen

2024 | 2023 | 2022 | 2021 | 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2007 | 2005

2024

Steinbrech Julian, Klein Till, Kirschke Stephanie, Mannell Hanna, Clau? Sebastian, Bertsche Thilo, Strobach Dorothea. Determining sensitivity and specificity of risk scores for QTc interval prolongation in hemato-oncology patients prescribed systemic antifungal therapy: a retrospective cross-sectional study. https://doi.org/10.1007/s11096-024-01788-w
BibTeX | RIS | DOI
Kipka Hannah, Liebchen Uwe, Hübner Max, H?fner Georg, Frey Otto, Wanner Klaus T., Kilger Erich, Hagl Christian, Tomasi Roland, Mannell Hanna. Serum concentrations of levosimendan and its metabolites OR-1855 and OR-1896 in cardiac surgery patients with cardiopulmonary bypass. https://doi.org/10.3389/fcvm.2024.1406338
PDF | BibTeX | RIS | DOI

2023

Golla Kathrin, Benesic Andreas, Mannell Hanna, Dreischulte Tobias, Grill Eva, Strobach Dorothea. Hepatic impairment as a risk factor for drug safety: suitability and comparison of four liver scores as screening tools. https://doi.org/10.3390/jcm12216814
PDF | BibTeX | RIS | DOI
Strobach Dorothea, Haimerl Lisa, Mannell Hanna, Stief Christian G., Karl Alexander, Grimm Tobias, Buchner Alexander. The characterization of non-oncologic chronic drug therapy in bladder cancer patients and the impact on recurrence-free and cancer-specific survival: a prospective study. https://doi.org/10.3390/jcm12216749
PDF | BibTeX | RIS | DOI
Kipka Hannah, Schaflinger Rebecca, Tomasi Roland, Pogoda Kristin, Mannell Hanna. The effects of the levosimendan metabolites OR-1855 and OR-1896 on endothelial pro-inflammatory responses. https://doi.org/10.3390/biomedicines11030918
PDF | BibTeX | RIS | DOI

2022

Hindelang V., Dimitriadis K., Saller T., Golla K., Mannell Hanna, Hug M. J., Strobach D.. A new medication-based prediction score for postoperative delirium in surgical patients: development and proof of feasibility in a retrospective patient cohort. https://doi.org/10.1691/ph.2022.2438
PDF | BibTeX | RIS | DOI
Mannell Hanna, Kameritsch Petra, Beck Heike, Pfeifer Alexander, Pohl Ulrich, Pogoda Kristin. Cx43 promotes endothelial cell migration and angiogenesis via the tyrosine phosphatase SHP-2. https://doi.org/10.3390/ijms23010294
PDF | BibTeX | RIS | DOI
Golla Kathrin, Mannell Hanna, Benesic Andreas, Dreischulte Tobias, Grill Eva, Strobach Dorothea. Feasibility of the MELD score as a screening tool for pharmacists to identify patients with impaired hepatic function at hospital admission. https://doi.org/10.1111/jcpt.13597
PDF | BibTeX | RIS | DOI
Haimerl Lisa, Strobach Dorothea, Mannell Hanna, Stief Christian G., Buchner Alexander, Karl Alexander, Grimm Tobias. Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer. https://doi.org/10.1007/s11096-021-01343-x
PDF | BibTeX | RIS | DOI
Kipka Hannah, Tomasi Roland, Hübner Max, Liebchen Uwe, Hagl Christian, Wanner Klaus T., Mannell Hanna, H?fner Georg. Simultaneous LC-ESI-MS/MS quantification of levosimendan and its metabolites for therapeutic drug monitoring of cardiac surgery patients. https://doi.org/10.3390/pharmaceutics14071454
PDF | BibTeX | RIS | DOI

2021

Seiberth Sarah, Bauer Dominik, Sch?nermarck Ulf, Mannell Hanna, Stief Christian, Hasford Joerg, Strobach Dorothea. Implementation of a renal pharmacist consultant service: information sharing in paper versus digital form. https://doi.org/10.1111/jcpt.13371
PDF | BibTeX | RIS | DOI

2020

Seiberth Sarah, Bauer Dominik, Sch?nermarck Ulf, Mannell Hanna, Stief Christian, Hasford Joerg, Strobach Dorothea. Correct use of non-indexed eGFR for drug dosing and renal drug-related problems at hospital admission. https://doi.org/10.1007/s00228-020-02953-6
PDF | BibTeX | RIS | DOI
Tahir Sibgha, Wagner Andreas H., Dietzel Steffen, Mannell Hanna, Pircher Joachim, Weckbach Ludwig T., Hecker Markus, Pohl Ulrich. Endothelial CD40 mediates microvascular von Willebrand factor-dependent platelet adhesion inducing inflammatory venothrombosis in ADAMTS13 knockout mice. https://doi.org/10.1055/s-0040-1702228
BibTeX | RIS | DOI
Kraemer Bjoern F., Geimer Marc, Franz-Wachtel Mirita, Lamkemeyer Tobias, Mannell Hanna, Lindemann Stephan. Extracellular matrix-specific platelet activation leads to a differential translational response and protein de novo synthesis in human platelets. https://doi.org/10.3390/ijms21218155
PDF | BibTeX | RIS | DOI
Immler Roland, Lange-Sperandio B?rbel, Steffen Tobias, Beck Heike, Rohwedder Ina, Roth Jonas, Napoli Matteo, Hupel Georg, Pfister Frederik, Popper Bastian, Uhl Bernd, Mannell Hanna, Reichel Christoph A., Vielhauer Volker, Scherberich Jürgen, Sperandio Markus, Pruenster Monika. Extratubular polymerized uromodulin induces leukocyte recruitment and inflammation in vivo. https://doi.org/10.3389/fimmu.2020.588245
PDF | BibTeX | RIS | DOI
Strobach Dorothea, Poppele Angelika, Mannell Hanna, Andraschko Monika, Schiek Susanne, Bertsche Thilo. Screening for impaired liver function as a risk factor for drug safety at hospital admission of surgical patients. https://doi.org/10.1007/s11096-019-00948-7
BibTeX | RIS | DOI
Heun Yvonn, Gr?ff Pascal, Lagara Aikaterini, Schelhorn Romina, Mettler Ramona, Pohl Ulrich, Mannell Hanna. The GEF cytohesin-2/ARNO mediates resistin induced phenotypic switching in vascular smooth muscle cells. https://doi.org/10.1038/s41598-020-60446-z
PDF | BibTeX | RIS | DOI

2019

Pogoda Kristin, Kameritsch P., Mannell Hanna, Pohl U.. Connexins in the control of vasomotor function. https://doi.org/10.1111/apha.13108
BibTeX | RIS | DOI
Kraemer Bjoern F., Mannell Hanna, Lamkemeyer Tobias, Franz-Wachtel Mirita, Lindemann Stephan. Heat-shock protein 27 (HSPB1) is upregulated and phosphorylated in human platelets during ST-elevation myocardial infarction. https://doi.org/10.3390/ijms20235968
PDF | BibTeX | RIS | DOI
Heun Yvonn, Pircher Joachim, Czermak Thomas, Bluem Philipp, Hupel Georg, Bohmer Monica, Kraemer Bjoern F., Pogoda Kristin, Pfeifer Alexander, Woernle Markus, Ribeiro Andrea, Hübner Max, Kreth Simone, Claus Ralf A., Weis Sebastian, Ungelenk Luisa, Kr?tz Florian, Pohl Ulrich, Mannell Hanna. Inactivation of the tyrosine phosphatase SHP-2 drives vascular dysfunction in sepsis. https://doi.org/10.1016/j.ebiom.2019.03.034
PDF | BibTeX | RIS | DOI
Rieck Sarah, Heun Yvonn, Heidsieck Alexandra, Mykhaylyk Olga, Pfeifer Alexander, Gleich Bernhard, Mannell Hanna, Wenzel Daniela. Local anti-angiogenic therapy by magnet-assisted downregulation of SHP2 phosphatase. https://doi.org/10.1016/j.jconrel.2019.05.031
BibTeX | RIS | DOI
Kameritsch Petra, Kiemer Felizitas, Mannell Hanna, Beck Heike, Pohl Ulrich, Pogoda Kristin. PKA negatively modulates the migration enhancing effect of Connexin 43. https://doi.org/10.1016/j.bbamcr.2019.02.001
BibTeX | RIS | DOI
Grundler Groterhorst Katharina, Mannell Hanna, Pircher Joachim, Kraemer Bjoern F.. Platelet proteasome activity and metabolism is upregulated during bacterial sepsis. https://doi.org/10.3390/ijms20235961
PDF | BibTeX | RIS | DOI
Heun Yvonn, Grundler Groterhorst Katharina, Pogoda Kristin, Kraemer Bjoern F., Pfeifer Alexander, Pohl Ulrich, Mannell Hanna. The phosphatase SHP-2 activates HIF-1α in wounds in vivo by inhibition of 26S proteasome activity. https://doi.org/10.3390/ijms20184404
PDF | BibTeX | RIS | DOI
Strobach Dorothea, Mannell Hanna. Tyrosinkinaseinhibitoren beeinflussen renale Transporter: was bedeutet das für die klinische Praxis?.
BibTeX | RIS

2018

Pircher Joachim, Czermak Thomas, Ehrlich Andreas, Eberle Clemens, Gaitzsch Erik, Margraf Andreas, Grommes Jochen, Saha Prakash, Titova Anna, Ishikawa-Ankerhold Hellen, Stark Konstantin, Petzold Tobias, Stocker Thomas, Weckbach Ludwig T., Novotny Julia, Sperandio Markus, Nieswandt Bernhard, Smith Alberto, Mannell Hanna, Walzog Barbara, Horst David, Soehnlein Oliver, Massberg Steffen, Schulz Christian. Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation. https://doi.org/10.1038/s41467-018-03925-2
PDF | BibTeX | RIS | DOI
Brettner Florian, Darling Joshua, Baeuml Edith-Cathrin, Mannell Hanna, Frank Hans-Georg, Amini Martina, Hulde Nikolai, Kammerer Tobias, Becker Bernhard F., Rehm Markus, Conzen Peter, Chappell Daniel. Chances and limitations of isolated mouse heart models for investigating the endothelial glycocalyx1. https://doi.org/10.3233/ch-170327
BibTeX | RIS | DOI

2017

Gaitzsch Erik, Czermak Thomas, Ribeiro Andrea, Heun Yvonn, Bohmer Monica, Merkle Monika, Mannell Hanna, Schulz Christian, W?rnle Markus, Pircher Joachim. Double-stranded DNA induces a prothrombotic phenotype in the vascular endothelium. https://doi.org/10.1038/s41598-017-01148-x
PDF | BibTeX | RIS | DOI
Heun Yvonn, Pogoda Kristin, Anton Martina, Pircher Joachim, Pfeifer Alexander, Woernle Markus, Ribeiro Andrea, Kameritsch Petra, Mykhaylyk Olga, Plank Christian, Kroetz Florian, Pohl Ulrich, Mannell Hanna. HIF-1α dependent wound healing angiogenesis in?vivo can be controlled by site-specific lentiviral magnetic targeting of SHP-2. https://doi.org/10.1016/j.ymthe.2017.04.007
PDF | BibTeX | RIS | DOI
Pogoda Kristin, Mannell Hanna, Blodow Stephanie, Schneider Holger, Schubert Kai Michael, Qiu Jiehua, Schmidt Andreas, Imhof Axel, Beck Heike, Tanase Laurentia Irina, Pfeifer Alexander, Pohl Ulrich, Kameritsch Petra. NO augments endothelial reactivity by reducing myoendothelial calcium signal spreading: a novel role for Cx37 (Connexin 37) and the protein tyrosine phosphatase SHP-2. https://doi.org/10.1161/atvbaha.117.309913
BibTeX | RIS | DOI
Heun Yvonn, Hildebrand Staffan, Heidsieck Alexandra, Gleich Bernhard, Anton Martina, Pircher Joachim, Ribeiro Andrea, Mykhaylyk Olga, Eberbeck Dietmar, Wenzel Daniela, Pfeifer Alexander, Woernle Markus, Kr?tz Florian, Pohl Ulrich, Mannell Hanna. Targeting of magnetic nanoparticle-coated microbubbles to the vascular wall empowers site-specific lentiviral gene delivery in vivo. https://doi.org/10.7150/thno.16192
PDF | BibTeX | RIS | DOI

2016

Blüm Philipp, Pircher Joachim, Merkle Monika, Czermak Thomas, Ribeiro Andrea, Mannell Hanna, Kr?tz Florian, Hennrich Alexander, Spannagl Michael, K?ppel Simone, Gaitzsch Erik, W?rnle Markus. Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C. https://doi.org/10.1038/cmi.2016.10
BibTeX | RIS | DOI
Chillo Omary, Kleinert Eike?Christian, Lautz Thomas, Lasch Manuel, Pagel Judith-Irina, Heun Yvonn, Troidl Kerstin, Fischer Silvia, Caballero-Martinez Amelia, Mauer Annika, Kurz Angela?R.M., Assmann Gerald, Rehberg Markus, Kanse Sandip?M., Nieswandt Bernhard, Walzog Barbara, Reichel Christoph?A., Mannell Hanna, Preissner Klaus?T., Deindl Elisabeth. Perivascular mast cells govern shear stress-induced arteriogenesis by orchestrating leukocyte function. https://doi.org/10.1016/j.celrep.2016.07.040
PDF | BibTeX | RIS | DOI
Grundler Katharina, Rotter Raffaela, Tilley Sloane, Pircher Joachim, Czermak Thomas, Yakac Mustaf, Gaitzsch Erik, Massberg Steffen, Kr?tz Florian, Sohn Hae-Young, Pohl Ulrich, Mannell Hanna, Kraemer Bjoern F. The proteasome regulates collagen-induced platelet aggregation via nuclear-factor-kappa-B (NF?B) activation. https://doi.org/10.1016/j.thromres.2016.10.009
BibTeX | RIS | DOI

2015

Merkle Monika, Pircher Joachim, Mannell Hanna, Kr?tz Florian, Blüm Philipp, Czermak Thomas, Gaitzsch Erik, Schneider Christine, K?ppel Simone, Ribeiro Andrea, W?rnle Markus. LL37 inhibits the inflammatory endothelial response induced by viral or endogenous DNA. https://doi.org/10.1016/j.jaut.2015.07.015
BibTeX | RIS | DOI
Alig Stefan K., Stampnik Yvonn, Pircher Joachim, Rotter Raffaela, Gaitzsch Erik, Ribeiro Andrea, W?rnle Markus, Kr?tz Florian, Mannell Hanna. The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α) protein levels in endothelial cells under hypoxia. https://doi.org/10.1371/journal.pone.0121113
PDF | BibTeX | RIS | DOI

2014

Pircher Joachim, Czermak Thomas, Merkle Monika, Mannell Hanna, Kr?tz Florian, Ribeiro Andrea, Vielhauer Volker, Nadjiri Jonathan, Gaitzsch Erik, Niemeyer Markus, Porubsky Stefan, Gr?ne Hermann-Josef, W?rnle Markus. Hepatitis C virus induced endothelial inflammatory response depends on the functional expression of TNFα receptor subtype 2. https://doi.org/10.1371/journal.pone.0113351
PDF | BibTeX | RIS | DOI
Mannell Hanna, Krotz Florian. SHP-2 regulates growth factor dependent vascular signalling and function. https://doi.org/10.2174/1389557514999140506094738
BibTeX | RIS | DOI

2013

Koch Elisabeth, Pircher Joachim, Czermak Thomas, Gaitzsch Erik, Alig Stefan, Mannell Hanna, Niemeyer Markus, Kr?tz Florian, W?rnle Markus. The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular haemostasis in TNFα-induced inflammation in vivo. https://doi.org/10.1155/2013/279781
PDF | BibTeX | RIS | DOI

2012

Pircher Joachim, Fochler Franziska, Czermak Thomas, Mannell Hanna, Kraemer Bjoern F., W?rnle Markus, Sparatore Anna, Del Soldato Piero, Pohl Ulrich, Kr?tz Florian. Hydrogen sulfide–releasing aspirin derivative ACS14 exerts strong antithrombotic effects in vitro and in vivo. https://doi.org/10.1161/atvbaha.112.300627
BibTeX | RIS | DOI
Pircher Joachim, Merkle Monika, W?rnle Markus, Ribeiro Andrea, Czermak Thomas, Stampnik Yvonn, Mannell Hanna, Niemeyer Markus, Vielhauer Volker, Kr?tz Florian. Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2. https://doi.org/10.1186/ar4064
PDF | BibTeX | RIS | DOI
Merkle Monika, Ribeiro Andrea, Belling Franziska, Mannell Hanna, Kr?tz Florian, Pircher Joachim, W?rnle Markus. Response of VEGF to activation of viral receptors and TNFα in human mesangial cells. https://doi.org/10.1007/s11010-012-1406-8
BibTeX | RIS | DOI
Mannell Hanna, Pircher Joachim, Fochler Franziska, Stampnik Yvonn, R?thel Thomas, Gleich Bernhard, Plank Christian, Mykhaylyk Olga, Dahmani Chiheb, W?rnle Markus, Ribeiro Andrea, Pohl Ulrich, Kr?tz Florian. Site directed vascular gene delivery in vivo by ultrasonic destruction of magnetic nanoparticle coated microbubbles. https://doi.org/10.1016/j.nano.2012.03.007
BibTeX | RIS | DOI
Merkle Monika, Ribeiro Andrea, K?ppel Simone, Pircher Joachim, Mannell Hanna, Roeder Maximilian, W?rnle Markus. TLR3-dependent immune regulatory functions of human mesangial cells. https://doi.org/10.1038/cmi.2012.3
BibTeX | RIS | DOI
Mannell Hanna, Pircher Joachim, R?thel Thomas, Schilberg Katharina, Zimmermann Katrin, Pfeifer Alexander, Mykhaylyk Olga, Gleich Bernhard, Pohl Ulrich, Kr?tz Florian. Targeted endothelial gene delivery by ultrasonic destruction of magnetic microbubbles carrying lentiviral vectors. https://doi.org/10.1007/s11095-012-0678-8
BibTeX | RIS | DOI

2011

Mannell Hanna, Pircher Joachim, Chaudhry Daniel I., Alig Stefan K.C., Koch Elisabeth G., Mettler Ramona, Pohl Ulrich, Kr?tz Florian. ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression. https://doi.org/10.1093/cvr/cvr265
BibTeX | RIS | DOI
R?thel T., Mannell Hanna, Pircher Joachim, Gleich B., Pohl Ulrich, Kr?tz F.. Magnetic stents retain nanoparticle-bound antirestenotic drugs transported by lipid microbubbles. https://doi.org/10.1007/s11095-011-0643-y
BibTeX | RIS | DOI

2010

Mannell Hanna, Hammitzsch Ariane, Mettler Ramona, Pohl Ulrich, Kr?tz Florian. Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt. https://doi.org/10.1016/j.cellsig.2009.09.015
BibTeX | RIS | DOI

2009

Krotz F., Hellwig N., Burkle M. A., Lehrer S., Riexinger T., Mannell Hanna, Sohn H.-Y., Klauss V., Pohl U.. A sulfaphenazole-sensitive EDHF opposes platelet-endothelium interactions in vitro and in the hamster microcirculation in vivo. https://doi.org/10.1093/cvr/cvp301
BibTeX | RIS | DOI
Struthmann L., Hellwig N., Pircher J., Sohn H.‐Y., Buerkle M.A., Klauss V., Mannell Hanna, Pohl U., Kr?tz F.. Prothrombotic effects of diclofenac on arteriolar platelet activation and thrombosis in?vivo. https://doi.org/10.1111/j.1538-7836.2009.03582.x
BibTeX | RIS | DOI

2007

Gleich Bernhard, Hellwig Nicole, Bridell Hanna, Jurgons Roland, Seliger Christian, Alexiou Christoph, Wolf Bernhard, Weyh Thomas. Design and evaluation of magnetic fields for nanoparticle drug targeting in cancer. https://doi.org/10.1109/tnano.2007.891829
BibTeX | RIS | DOI
Mannell Hanna, Hellwig Nicole, Gloe Torsten, Plank Christian, Sohn Hae-Young, Groesser Leopold, Walzog Barbara, Pohl Ulrich, Kr?tz Florian. Inhibition of the tyrosine phosphatase SHP-2 suppresses angiogenesis in vitro and in vivo. https://doi.org/10.1159/000110081
BibTeX | RIS | DOI
Kro?tz Florian, Sohn Hae-Young, Mannell Hanna. Letter by Kro?tz et al regarding article, “Improvement of peripheral endothelial dysfunction by protein tyrosine phosphatase inhibitors in heart failure”. https://doi.org/10.1161/circulationaha.107.690354
BibTeX | RIS | DOI
Mannell Hanna, Krotz Florian. The role of SHP-2 in cell signalling and human disease. https://doi.org/10.2174/157340807782330264
BibTeX | RIS | DOI

2005

Kr?tz Florian, Engelbrecht Barbara, Buerkle Martin A., Bassermann Florian, Bridell Hanna, Gloe Torsten, Duyster Justus, Pohl Ulrich, Sohn Hae-Young. The tyrosine phosphatase, SHP-1, is a negative regulator of endothelial superoxide formation. https://doi.org/10.1016/j.jacc.2005.02.039
BibTeX | RIS | DOI

拉斯维加斯赌城